Currently, for the purpose of treating the arthritis, a variety of transdermal preparations containing non-steroidal anti-inflammatory drugs such as ketoprofen, diclofenac, flurbiprofen, felbinac, piroxicam and the like were developed and are marketed. Many researches on the transdermal preparations are carried out to meet the market needs. Main research fields include a research on the permeation enhancement of drug for more rapid and effective treatment, a research on the decrease of skin trouble caused by a patch type product, a research on adhesive substances not causing pains when the patch is detached after use, and the like.
The typical transdermal preparations containing the non-steroidal anti-inflammatory drugs, which are used for the purpose of the arthritis treatment, can directly deliver the drug in an inflamed area. The transdermal preparations directly deliver the drug to a lesion to maintain a concentration in the synovial fluid, on which the drugs act, at ⅕˜½ of a level in the oral administration. Accordingly, the transdermal preparations exhibit the effects similar to the oral administration and the drug concentration in the blood is lower by about 100 times than the oral preparations, so that they do not cause the side effects such as gastrointestinal tract disorder. Owing to such advantages, the transdermal preparations containing the non-steroidal anti-inflammatory drugs are widely used. However, they are still considered to have the efficacies lower than the oral preparations. Therefore, if a concentration of drug in the lesion such as synovial fluid can be increased as much as the oral preparation by improving a drug permeation, it is possible to obtain a treatment effect same as that of the oral preparation without causing the side effects of the non-steroidal anti-inflammatory drugs such as gastrointestinal tract disorder, which is expected to be more effective for the arthritis treatment.
In the transdermal preparation fields of a drug-in-adhesive type, as technology for increasing the drug permeation, it is widely used a technology for using permeation enhancer to increase diffusion and distribution effects of the drug, containing the drug at a saturation concentration in a system to increase a chemical activity of the drug, or hydrating the skin to lower barrier function of skin for the drug, thereby easily diffusing the drug.
As a specific example, a Korean Patent No. 10-0213465 discloses a multi-layered patch for obtaining high drug permeability. The patch uses an elastic backing and comprises an adhesive layer for adhering the backing and a drug layer, the drug layer containing the drug of a high concentration adding polyvinyl pyrrolidone or ethylene-vinylacetate and an adhesive layer for providing an adhesion and controlling a drug release, thereby obtaining high drug permeability and the skin adhesion. However, it is not easy to produce such patch because it has a multi-layered structure. In addition, since the adhesive layers are separately provided to give the adhesion, the drug permeation is slow, thereby exhibiting the limited effect only.
A Korean Patent No. 10-0188180 discloses technologies for increasing the drug permeability into the skin using multi-layered structure that is composed acrylic adhesives having difference water-absorption capacity and each acrylic adhesives layer can be changed drug solubility by water discharged from skin.
According to one technology suggested, plural adhesive layers consisting of acrylic adhesives resins having different water-absorption capacity are adapted to contain the drug and an acrylic adhesive layer having a low water-absorption capacity is located at the lowest layer. Thereby, although the content of the drug is decreased as the initial drug is permeated into the skin, the water moves to the upper layer and decrease the drug solubility in the upper acrylic adhesive layer, so that the drug is supplied to the lowest layer by concentration gradation of drug. As a result, the drugs are continuously delivered to the skin.
According to another technology suggested in the above patent, the acrylic adhesive layer having a high water-absorption capacity is located at the lowest layer, the drug of a high concentration is initially permeated and the drug permeation is decreased as time goes by, so that the drug is constantly permeated into skin. According to the first technology, since only the acrylic adhesive layers having similar solubility for the drug are used, a concentration difference of drug between acrylic adhesives layers is small, so that a desired effect is little. In addition, the concentration difference of drug in the adhesive layers is decreased during long time storage, so that a desired effect cannot be achieved. According to the second technology, when the acrylic adhesive layer having a high water-absorption capacity is located at the lowest layer, the hydrophobic drug contained in the upper layer is not smoothly moved to lower layer, so that the high drug permeability cannot be obtained.
In addition, U.S. Pat. No. 6,676,962 discloses a transdermal preparation containing a non-steroidal anti-inflammatory drug having a carboxyl group as an active material, having a unidirectional or dual directional flexibility due to a backing inactive for the active agent and using an acrylic adhesives base. In particular, according to the technology suggested, in consideration of use convenience, the flexible woven-fabric, knitted fabric, non-woven fabric or flexible foam (PE, PVC, EVA) as a backing is adopted so that it is easily used in the joint region and it is possible to obtain the higher drug permeability when the foam is adopted.
According to U.S. Pat. No. 5,702,720, the polyvinyl pyrrolidone which is hydrophilic polymer is used so that the water, which is exuded from the skin, is easily discharged to the outside and the physical properties of the patch is not deteriorated. In particular, the polyvinyl pyrrolidone, which is hydrophilic polymer, is used so that the pain caused when the patch is detached is decreased and the cohesion for preventing the adhesives from being remained is increased, among the properties of the patch.
According to Korean Patent Un-examined Publication No. 2002-035451 disclosing a transdermal preparation containing the diclofenac diethylammonium, the polyvinyl pyrrolidone, which is hydrophilic polymer, is used to absorb the water discharged from the skin, such as sweat, thereby enabling the patch not to be easily detached during the attachment and preventing the adhesive from being remained when detaching the patch. In addition to the prior arts as mentioned above, many technologies are disclosed in the fields. However, it is still needed a patch achieving the high permeability of drug in a short time and maintaining the high permeability of drug to maximize the treatment effect, increasing an adaptive degree of a patient due to an optimized adhesion property and enabling the patch to be easily produced. The invention is provided to meet the requirements.